MI Flashcards
Risks for Atherosclerosis
- Age, sex (male), total cholesterol, HDL cholesterol, smoking, DM, HTN, family history of premature CVD (Framingham heart study)
- inter heart study then added: abdominal obesity, psychosocial index, Apo A/B ratio, exercise, alcohol (which actually seen to be protective)
- newer risks: CRP, lipoprotein A (inherited risk factor, elevated in 20% of the population), chronic loud noise exposure, sedentarism
- inflammation is a risk! SLE, RA, psoriasis, IBD, COPD, HIV, etc.
CVD in developing countries
- low education has greater impact on CVD risk in low income countries
- majority of CVD deaths are in lower income countries
Framingham risk score
Low - <10% 10 year risk
Intermediate - 10-20% 10 year risk
High - >20%10 year risk
Who can benefit from statins?
- LDL over 5, DM, CKD, ASCVD
- people with increased systemic inflammation but normal cholesterol
How does stress affect CVD?
- increases SNS/ HPA axis/ HTN/ insulin resistance
Cholesterol
- made by all cells except mature RBCs
- major constituent of plaque
- component of cell membranes, steroid and bile acid synthesis
input: diet and synthesis
output: bile acids and biliary cholesterol
Triglycerides
- main dietary and endogenous fat
- main source of immediate and stored energy
- carried by chylomicrons and VLDLs
- water insoluble lipid that must be solubilized and transported by lipoproteins (along with cholesterol)
Size of lipoproteins and their respective compositions
- chylomicrons < VLDLs < LDLs < HDLs
- smaller are more triglycerides, larger are more cholesterol/ phospholipids/ proteins
Journey of fat through the body
Different methods of entry into SI?
- Emulsified fats are digested by lipase/ co-lipase
- Cholesterol esters are digested by pancreatic lipase/ co-lipase into cholesterol and FFAs
- monoglycerides and FFAs diffuse into SI
- cholesterol enters via NPC1L1 transporter
- these products are re-combined to form chylomicrons, which travel through the body via lymph
Role of lipoprotein lipase (LPL)
- sits on capillaries to digest TGs and deliver FAs to issues for energy (similar role in VLDL catabolism)
Role of VLDL
- body’s means of delivering FAs to tissues for energy, even when fasting
- synthesized by the liver using MTP
How is LDL broken down?
- binds to LDL receptors and internalized
- hydrolyzed in a lysosome into cholesterol and amino acids
- results in decreased HMG CoA reductase, decreased LDL receptors, and increased ACAT (produces cholesterol oleate with excess cholesterol)
Definition of dyslipidemia
Primary vs secondary
- increased cholesterol and/or triglycerides and/or low HDL-C
- Primary - genetic, often severe lipid elevations (cholesterol over 6.5 and LDL-C over 4.5 and TG over 3)
- Secondary - diet/ obesity/ DM/ etc, often minor elevations
Signs of genetic hyperlipidemia?
- tendon/ palmar/ eruptive xanthomas
- xanthelasma
- corneal arcus
Examples of genetic dyslipidemia
- Familial hypercholesterolemia - mutations in LDL receptor/apoB, increased function of PCSK9
- Dysbetalipoprotenemia - apoE2:E2 and overproduction of VLDL
- Lipoprotein lipase deficiency - no LPL activity
- Tangier disease - no ABCA1 activity (responsible for HDL formation)
Fat targets if low/ med/ high risk?
Low risk - LDL under 2.5, ApoB under 0.85, non HDL under 3.2
Med risk - LDL under 2, ApoB under 0.8, non HDL under 2.6
High risk - LDL under 1.8, ApoB under 0.7, non HDL under 2.4
Preferred fuel of heart when fasting?
What does the myocardium depend on?
- FFAs
- totally relies on aerobic metabolism (need enough ATP for cross bridge cycling in sarcomeres, can only be achieved if O2 is present)
What does the LMCA supply?
(originates from L sinus of valsalva)
- L anterior descending supplies anterior wall of the L ventricle and most of the inter ventricular septum
- Circumflex supplies the lateral wall of the L ventricle
What does the RCA supply?
(originates from the R sinus of valsalva)
- SA and AV nodes
- RV and posterior inter ventricular septum
What are the conductance vs resistance vessels of the heart?
Conductance - epi/myocardial penetrating vessels
Resistance - arterioles and pre-capillary sphincters
How is coronary flow affected by diastole? With ischemia, which part of the heart suffers first?
- coronary flow to the LV is almost ALL diastolic
- in systole, aortic root pressure is equal to LV pressure, thus almost no coronary flow
- diastolic root pressure is higher than diastolic LV pressure, and so duration of diastole is important
- endocardial ischemia will occur earlier and more severely
*Coronary perfusion gradient = aortic root pressure - LV pressure
Methods of Coronary resistance?
1 metabolic - ischemia increases adenosine, H/K/CO2/ decreased O2 that all lead to vasodilation
- endothelial - production of NO/ prostacyclin (dilates) and endothelin (constricts)
- neurogenic - SNS (constricts) and PNS (dilates)
- myogenic - pressure/ flow sensitive smooth muscle in arteriolar walls
What can cause an increase in O2 demand?
- bigger radius (preload)
- bigger intraventricular pressure (impedence)
- increased HR
- increased contractility
*interestingly, a thicker wall requires less O2
What is the law of LaPlace?
Force in ventricular wall = (pressure x radius)/ 2x wall thickness
What is coronary reserve?
difference between resting coronary flow and maximum coronary flow
What leads to the chest discomfort experienced in angina?
Adenosine –> vasodilation
When is flow reduced in atherosclerosis?
70% - reduction of flow
75% - angina
90% - cannot increase flow to meet demands
What is an example of an acute rise of demand vs chronic?
Acute reduction of supply vs chronic?
Acute demand - exercise
Chronic demand - anemia, respiratory failure, CHF, shunt, HTN
Acute supply - MI
Chronic supply - atherosclerosis
Where does atherogenesis most commonly occur?
- occurs in the arterial intima (superficial to media and adventitia)
- bends and branches w low shear forces/ turbulence and non-laminar flow (i.e. lesser curve of aorta)
Role of endothelial cells
- tight junctions act as a barrier to protect sub endothelial space
- make mediators that maintain a non-thrombotic lumen, maintain sm cell relaxed state
ECM composition
- fibrillar collagen (strength), proteoglycans and elastin (flexibility)
Process of artherogenesis
- loss of endothelial cell alignment results in increased permeability and increased leukocyte adhesion molecules (ICAM/ VCAM/ P-selectin)
- sub endothelial chemokine promote diapedesis of WBCs into sub endothelial space
- monocytes retain lipids, resulting in macrophage foam cells
- macrophages express scavenger proteins that uptake mLDL to the point of destruction, resulting in cholesterol/ crystal spillage and inflammation
How are smooth muscle cells affected in atherosclerosis?
- increased endothelin and angiotensin II and decreased prostacyclin/NO results in constriction
- more IL-6, TNF-A, PAI-1 and tissue factor (inflammation)
- proliferate and migrate to sub endothelial space, produce free radicals, synthesize excess ECM, fibrous cap formation
Vulnerable vs. Stable plaque
Vulnerable - large lipid/ necrotic core, few sm cells, thin fibrous cap, little ECM, many foam cells esp. in shoulder, proteases, big plaque
Stable - thick fibrous cap, less lipids, fewer inflamm cells, dense ECM
*can be achieved by decreased LDL/BP/ATII and increasing HDL
Optimal therapy for atherosclerosis
- ASA (decrease platelet activity)
- statins/ezetimibe/PCSK9 inhibitors (reduce cholesterol)
- no smoking (reduces oxidized LDL, platelets, sm constriction)
- DM therapy (reduces irritating glycated products)
- exercise (increases laminar shear)
- anti-hypertensives (reduces barotrauma and ox radicals)
Chest pain criteria for angina
- Substernal chest discomfort with characteristic quality and duration
- Provoked by exertion/ emotional distress
- Relieved promptly by rest or nitroglycerin
*consider other causes if males under 40 and females under 60 with few risks, but test anyway if over these ages or severe/ multiple risks
Ischemic symptoms
- chest pain, dyspnea, shoulder/arm/hand/jaw/neck pain, nausea/ vomiting, diaphoresis, presyncope, arrhythmia
Prognostic factors for stable CAD
- anatomical distribution/ burden
- ischemic burden
- LVEF and wall motion abnormalities
Criteria for myocardial injury (i.e. HF, myocarditis) vs. acute MI?
injury –> elevated cardiac tropnin
acute MI –> evidence of ischemia on ECG, rise and fall of troponin, pathological Q waves, loss of myocardium or wall motion abnormalities
Unstable angina vs. non ST elevation MI vs. ST elevation MI
unstable angina –> transient acute ischemia not resulting in myocardial injury
- typical sx, negative biomarkers, +/- ischemia on ECG
Non-ST MI –> subendocardial ischemia resulting in myocardial injury
- typical sx, positive biomarkers, +/- ischemia on ECG
ST MI –> acute transmural ischemia (occlusive thrombus) resulting in MI and ECG changes
- typical sx, ECG changes, +/- imaging of ischemia
- do not need biomarkers for initial diagnosis
What are ischemic biomarkers? when do they peak?
- troponin I - cardiac myocytes
- troponin T - cardiac myocytes and some skeletal muscle
- creatine kinase - cytosol of most myocytes
- creatine kinase-MB isoenzyme - specific to cardiac myocytes
- myoglobin (muscle cells)
- AST (myocytes and hepatocytes)
- LDH (erythrocytes, muscle, kidneys, brain)
*linear peak at 1-2 days post AMI
Type I MI vs. Type II
1 - plaque rupture/ erosion
2 - severe HTN/ sustained tachyarrythmis
Stable vs unstable CAD?
Stable - predictable and low mortality, at least 70% lesion
Unstable - higher mortality, can be any size
How does an MI kill you?
- Mechanical VSD - short term, prevent with B-blocker and treat w surgery
- Heart failure - long term, prevent with LV enhancers, treat with transplant
Recurrent MI - long term, prevent via risk factors, treat w revascularization
Ventricular arrythmias - prevent with B-blockers and LVEF preservation, treat with ICD
Ways to help supply/demand/ cardioprotection?
Supply - antithrombotics and antiplatelets (prevent re-occlusion)
Demand - anti-ischemics
Cardioprotection - anti-arrythmics and anti-inflammatories
Examples of antiplatelets and antithrombins used to prevent MI?
antiplatelet - ASA (aspirin) - inhibits TXA2 which activates platelets
- ticagrelor (collagen), voraxapar (thrombin), clopidogrel, prasugrel
antithrombin - unfractionated heparin - prevents conversion of fibrinogen to fibrin
- LMWH, fondaparinux (factor X),
* DOACs (rivaroxaban, apixaban, dabigatran are NOT used as they bleed you out!)
Treatment if PI due to STEMI
- dual antiplatelet therapy for 1 year (ASA and clopidogrel)
- if after 1 year high risk of bleed -> SAPT or clopidorel
- if low risk of bleed -> DAPT up to 3 years
When should angiography be done?
- only if medium risk (DM, CKD, EF <40%, PCI in last 6 months)
- urgent only if high risk (elevated troponin, ST depression, T wave inversion, refractory angina, sx of heart failure, arrythmias)
What should the initial anticoagulant given be?
IV heparin in invasive, fondaparinux if conservative (though avoid if PCI in the next 7 days)
Medications to:
- lower afterload
- lower contractility
- lower HR
- lower preload
- increase fibrillatory threshold
afterload - Ca blocker, B-blocker, RAS antagonists
contractility and HR - Ca blocker, B-blocker
preload - diuretic, nitroglycerin
fibrillary threshold - B–blocker
Sx of acute MI
- chest pain radiating to both arms, 3rd heart sound, hypotension
- women and elderly can present with R-sided chest pain, abnormal T waves, normal physical exam and troponin (always do serial troponins)
Sx of acute thoracic aortic dissection
- acute chest/ back pain and pulse differential in upper extremities, wide mediastinum, sinus tach
Heart healthy diet
- avoid saturated fats (ideally under 9%)
- mediterranean diet, DASH diet (lowers both systolic and diastolic BP), portfolio diet
Signs of a STEMI on ECG?
- ST elevation in leads that overlie the affected tissue
- often reciprocal ST depression in opposite leads
- if a patient has had an MI before, they will have a pathological Q wave (inverted)
Signs of ischemia on ECG?
- ST depression or T wave flattening/ inversion
- changes do not localize to an anatomical location
Signs of pericarditis on ECG?
- see diffuse ST elevation, diffuse PR depression, and PR elevation in aVR
Which leads correspond to which anatomical region of the heart?
Inferior - II, III, aVF
Anteroseptal - V1, V2
Anterior - V3, V4
Lateral - V5, V6
Consequences of an inferior STEMI?
- hypotension, mitral regurgitation, complete heart block
